Cartilage InjuryPhase 3NCT01041001
Study to Compare Efficacy and Safety of Cartistem and Microfracture in Patients With Knee Articular Cartilage Injury
A Phase 3 study testing Cartistem and Microfracture treatment in people with Cartilage Injury and Osteoarthritis, run by Medipost Co Ltd. at 8 sites in South Korea.
Trial summary
The purpose of the study is to assess and compare the safety and efficacy of the allogeneic-unrelated umbilical cord blood-derived mesenchymal stem cell product (Cartistem®) to that of a microfracture treatment in patients with articular cartilage defect or injury. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cartilage Injury, Osteoarthritis
- What is being tested?
- Cartistem and Microfracture treatment
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 104 participants
- Where
- 8 sitesSouth Korea
- Study dates
- Feb 2009to Jan 2011
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with knee joint cartilage defect or injury of ICRS (International Cartilage Repair Society) Grade 4 confirmed by arthroscopy (At screening, patients diagnosed as such with an MRI may be included)
- Male or female patients at least 18 years of age
- Patients whose lesion (unilateral joint) is 2 ㎠ ~ 9㎠ in size
- Patients with articular swelling, tenderness and active range of motion of Grade 2 or below
- Patients with pain in affected joint of 60-mm or below on a 100-mm VAS (visual analogue scale)
- Patients with adequate blood coagulation activity, PT(INR) < 1.5, APTT <1.5×control
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- Patients with adequate renal function, Creatinine ≤ 2.0 ㎎/㎗, levels of proteinuria measured with Dipstick: trace or less
- Patients with adequate hepatic function, Bilirubin ≤ 2.0 ㎎/㎗, AST/ALT ≤ 100 IU/L
- Patients who have received no surgery or radiation therapy in the affected joint within the past 6 six weeks, and have recovered from the side effects of such past treatments
- Female patients of childbearing potential must agree to practice adequate methods of birth control to prevent pregnancy during the study
- Patients whose physical examination results show no ligament instability of Grade II or above (Grade 0: none, Grade I: 0-5 mm, Grade II: 5-10 mm, Grade III: >10 mm)
- Patients who voluntarily agreed to enroll in the study and signed an informed consent form
Who cannot join
- Patients with autoimmune disease or the medical history
- Patients with infections requiring parenteral administration of antibiotics
- Patients with myocardial infarction, ischemic heart failure, other serious heart conditions or uncontrolled hypertension, or any medical history of such diseases
- Patients with serious internal diseases
- Patients who are currently pregnant or nursing
- Patients with psychotic diseases, epilepsy, or any history of such diseases
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- Patients with alcohol abuse
- Patients who smoke excessively
- Patients with chronic inflammatory articular diseases such as rheumatoid arthritis
- Patients who were enrolled in any other clinical trials within the past four weeks
- Patients who had been administered with immunosuppressants such as Cyclosporin A or azathioprine within the past six weeks
- Patients whose physical examination results show ligament instability of Grade II or above (Grade 0: none, Grade I: 0-5 mm, Grade II: 5-10 mm, Grade III: >10 mm)
- Patients with a known history of hypersensitivity/allergy to gentamicin
- Patients who the principal investigator considers inappropriate for the clinical trial due to any other reasons than those listed above
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
South Korea8 sites
Gachon University Gil Hospital
Incheon, Gyunggido, 405-760
Inha University Hospital
Incheon, 400-711
Hanyang University Medical Center
Seoul, 133-792
Seoul Veterans Hospital
Seoul, 134-060
Samsung Medical Center
Seoul, 135-710
Asan Medical Center
Seoul, 138-736
Korea University Guro Hospital
Seoul, 152-703
Ewha Womans University Mokdong Hospital
Seoul, 158-710
About this study
Official title: Randomized, Open-Label, Multi-Center and Phase 3 Clinical Trial to Compare the Efficacy and Safety of Cartistem® and Microfracture in Patients With Knee Articular Cartilage Injury or Defect
The purpose of the study is to assess and compare the safety and efficacy of the allogeneic-unrelated umbilical cord blood-derived mesenchymal stem cell product (Cartistem®) to that of a microfracture treatment in patients with articular cartilage defect or injury.
Read the detailed description
The cartilage is a unique avascular, aneural tissue that does not regenerate easily once damaged. Chondral defects or damages to articular cartilages due to accidents, necrosis of subchondral bone tissue, or arthritis have become some of the more common disorders today. About 15% of the world's population is reportedly suffering from cartilage and joint damages such as degenerative arthritis and rheumatoid arthritis. As population aging progresses and as more young people start taking up active sports, the size of the target patient group is also growing. However, despite ongoing research, an effective treatment for cartilage defects is yet to be discovered. Various different types of treatments are currently in use, such as drug therapy, arthroscopy, and artificial joint surgery. However, they all fail to address the root cause. Complete treatment, or regeneration of damaged or defective cartilage is impossible and continuous drug administration or secondary surgeries are required in many cases.
As a way of regenerating the damaged or defective cartilage tissue, treatment of localized damage to articular cartilage using autologous chondrocytes is currently under review. A few life science companies both home and abroad are marketing this method of treatment called 'autologous chondrocyte transplant'. The treatment involves the extraction of healthy cartilage tissue from the patient which is then cultured and transplanted into the damaged site.
However, this treatment requires the extraction of chondrocytes directly from the patient and thus causes trauma in healthy articular cartilage. Also, this type of treatment cannot be applied to large lesions, nor is the efficacy satisfactory in patients over the age of 40 whose cellular activation levels are low. Thus, autologous chondrocyte transplant is rather limited in the number of cells harvested and their activation level and is therefore restricted in terms of treatment site, severity of the condition, and the size of lesion. The current technology allows the application of treatments in local cartilage defects but not in degenerative arthritis or rheumatoid arthritis. The technology needs to be taken up to another level in order to benefit such prevalent arthritic disorders. Treatments using stem cells do not cause damage to healthy articular cartilage as they don't require the harvesting of healthy cartilage tissues from the patients. Moreover, the number of successfully cultured cells is larger due to the excellent proliferation capability of stem cells and thus, mass supply is possible.
This clinical trial for the stem cell therapies is essential because treatment of cartilage defects with umbilical cord blood-derived mesenchymal stem cells, known to have the highest level of activity among all adult stem cells, opens the possibility of articular cartilage regeneration even for aged patients and patients with large lesions unable to benefit from existing treatments.
The biggest challenge faced by nations competing in the field of "tissue differentiation and regeneration using stem cells" is the question of whether or not the use of embryonic stem cells is ethical. Chondrogenesis using umbilical cord blood-derived mesenchymal stem cells can not only avoid similar challenges, but also present an innovative treatment mode with significant clinical implications for the patients.
In the clinical study, mesenchymal stem cells will be isolated from umbilical cord blood and cultured, mixed with semi- solid polymer, and administered into the cartilage tissue lesion by orthopedic surgery in order to stimulate the regeneration of defective cartilage tissue and to improve their functions.
- Conditions
- Cartilage Injury, Osteoarthritis
- Being tested
- Cartistem, Microfracture treatment
- Keywords
- Umbilical Cord Blood, Mesenchymal Stem Cells, cartilage injury, osteoarthritis
- Medical subject headings
- Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CartistemBiological
allogeneic-unrelated umbilical cord blood-derived mesenchymal stem cell product
Microfracture treatmentProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Cartistem | Experimental | A single dose of 500㎕/㎠ of cartilage defect Receives: Biological: Cartistem |
| Microfracture treatment | Active comparator | Not described Receives: Procedure: Microfracture treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
ICRS Cartilage Repair Assessment will follow to determine the appropriate grade. The treatment will be considered efficacious if the ICRS grade drops by at least 1 grade or more from baseline to week 48.
Measured: Week 0 and 48
Secondary outcomes (5)
Degree of improvement in the grade of joint pain measured on a 100-mm VAS (Visual Analogue Scale)
Measured: Week 0, 2, 4, 8, 12, 24, 36 and 48
Grade of cartilage regeneration in patients who agreed to a biopsy during arthroscopy at week 48
Measured: Week 48
Changes in WOMAC scores
Measured: Week 0, 2,4,8,12,24,36 and 48
Changes in IKDC Subjective Score
Measured: Week 0, 2, 4, 8, 12, 24, 36 and 48
ICRS scores
Measured: Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2009 (estimated)
- Study startFeb 2009
- Primary completionDec 2010
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cartilage InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 104 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medipost Co Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Hong-chul Lim, MD, PhD, Principal investigator, Korea University Guro Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01041001
- Sponsor's protocol ID
- MP-CRP-005
- Status last verified
- Apr 2012
- First submitted
- 29 Dec 2009
- Last updated
- 20 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Lim HC, Park YB, Ha CW, Cole BJ, Lee BK, Jeong HJ, Kim MK, Bin SI, Choi CH, Choi CH, Yoo JD; Cartistem Research Group; Yoon JR, Chung JY. Allogeneic Umbilical Cord Blood-Derived Mesenchymal Stem Cell Implantation Versus Microfracture for Large, Full-Thickness Cartilage Defects in Older Patients: A Multicenter Randomized Clinical Trial and Extended 5-Year Clinical Follow-up. Orthop J Sports Med. 2021 Jan 12;9(1):2325967120973052. doi: 10.1177/2325967120973052. eCollection 2021 Jan.
PubMed 33490296
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Open-Label, Multi-Center and Phase 3 Clinical Trial to Compare the Efficacy and Safety of Cartistem® and Microfracture in Patients With Knee Articular Cartilage Injury or Defect
- ClinicalTrials.gov ID
- NCT01041001
- Acronym / sponsor ID
- MP-CRP-005
- Conditions
- Cartilage Injury, Osteoarthritis
- Keywords
- Umbilical Cord Blood, Mesenchymal Stem Cells, cartilage injury, osteoarthritis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- Medipost Co Ltd.Industry (pharma, biotech, devices)
- Study start
- Feb 2009
- Primary completion
- Dec 2010 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 30 Dec 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to assess and compare the safety and efficacy of the allogeneic-unrelated umbilical cord blood-derived mesenchymal stem cell product (Cartistem®) to that of a microfracture treatment in patients with articular cartilage defect or injury.
Detailed description
The cartilage is a unique avascular, aneural tissue that does not regenerate easily once damaged. Chondral defects or damages to articular cartilages due to accidents, necrosis of subchondral bone tissue, or arthritis have become some of the more common disorders today. About 15% of the world's population is reportedly suffering from cartilage and joint damages such as degenerative arthritis and rheumatoid arthritis. As population aging progresses and as more young people start taking up active sports, the size of the target patient group is also growing. However, despite ongoing research, an effective treatment for cartilage defects is yet to be discovered. Various different types of treatments are currently in use, such as drug therapy, arthroscopy, and artificial joint surgery. However, they all fail to address the root cause. Complete treatment, or regeneration of damaged or defective cartilage is impossible and continuous drug administration or secondary surgeries are required in many cases.
As a way of regenerating the damaged or defective cartilage tissue, treatment of localized damage to articular cartilage using autologous chondrocytes is currently under review. A few life science companies both home and abroad are marketing this method of treatment called 'autologous chondrocyte transplant'. The treatment involves the extraction of healthy cartilage tissue from the patient which is then cultured and transplanted into the damaged site.
However, this treatment requires the extraction of chondrocytes directly from the patient and thus causes trauma in healthy articular cartilage. Also, this type of treatment cannot be applied to large lesions, nor is the efficacy satisfactory in patients over the age of 40 whose cellular activation levels are low. Thus, autologous chondrocyte transplant is rather limited in the number of cells harvested and their activation level and is therefore restricted in terms of treatment site, severity of the condition, and the size of lesion. The current technology allows the application of treatments in local cartilage defects but not in degenerative arthritis or rheumatoid arthritis. The technology needs to be taken up to another level in order to benefit such prevalent arthritic disorders. Treatments using stem cells do not cause damage to healthy articular cartilage as they don't require the harvesting of healthy cartilage tissues from the patients. Moreover, the number of successfully cultured cells is larger due to the excellent proliferation capability of stem cells and thus, mass supply is possible.
This clinical trial for the stem cell therapies is essential because treatment of cartilage defects with umbilical cord blood-derived mesenchymal stem cells, known to have the highest level of activity among all adult stem cells, opens the possibility of articular cartilage regeneration even for aged patients and patients with large lesions unable to benefit from existing treatments.
The biggest challenge faced by nations competing in the field of "tissue differentiation and regeneration using stem cells" is the question of whether or not the use of embryonic stem cells is ethical. Chondrogenesis using umbilical cord blood-derived mesenchymal stem cells can not only avoid similar challenges, but also present an innovative treatment mode with significant clinical implications for the patients.
In the clinical study, mesenchymal stem cells will be isolated from umbilical cord blood and cultured, mixed with semi- solid polymer, and administered into the cartilage tissue lesion by orthopedic surgery in order to stimulate the regeneration of defective cartilage tissue and to improve their functions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cartistem | Experimental | Biological: CartistemA single dose of 500㎕/㎠ of cartilage defect |
| Microfracture treatment | Active comparator | Procedure: Microfracture treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients with knee joint cartilage defect or injury of ICRS (International Cartilage Repair Society) Grade 4 confirmed by arthroscopy (At screening, patients diagnosed as such with an MRI may be included)
- Male or female patients at least 18 years of age
- Patients whose lesion (unilateral joint) is 2 ㎠ ~ 9㎠ in size
- Patients with articular swelling, tenderness and active range of motion of Grade 2 or below
- Patients with pain in affected joint of 60-mm or below on a 100-mm VAS (visual analogue scale)
Key exclusion criteria (14 listed)
- Patients with autoimmune disease or the medical history
- Patients with infections requiring parenteral administration of antibiotics
- Patients with myocardial infarction, ischemic heart failure, other serious heart conditions or uncontrolled hypertension, or any medical history of such diseases
- Patients with serious internal diseases
- Patients who are currently pregnant or nursing
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cartistemallogeneic-unrelated umbilical cord blood-derived mesenchymal stem cell product | Biological | Cartistem |
| Microfracture treatment | Procedure or surgery | Microfracture treatment |
Primary outcome
ICRS Cartilage Repair Assessment will follow to determine the appropriate grade. The treatment will be considered efficacious if the ICRS grade drops by at least 1 grade or more from baseline to week 48.
Time frame: Week 0 and 48
5 secondary outcomes
Degree of improvement in the grade of joint pain measured on a 100-mm VAS (Visual Analogue Scale)
Time frame: Week 0, 2, 4, 8, 12, 24, 36 and 48
Grade of cartilage regeneration in patients who agreed to a biopsy during arthroscopy at week 48
Time frame: Week 48
Changes in WOMAC scores
Time frame: Week 0, 2,4,8,12,24,36 and 48
Changes in IKDC Subjective Score
Time frame: Week 0, 2, 4, 8, 12, 24, 36 and 48
ICRS scores
Time frame: Week 48
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2017.
- Derived from this study: PubMed 33490296Lim HC, Park YB, Ha CW, Cole BJ, Lee BK, Jeong HJ, Kim MK, Bin SI, Choi CH, Choi CH, Yoo JD; Cartistem Research Group; Yoon JR, Chung JY. Allogeneic Umbilical Cord Blood-Derived Mesenchymal Stem Cell Implantation Versus Microfracture for Large, Full-Thickness Cartilage Defects in Older Patients: A Multicenter Randomized Clinical Trial and Extended 5-Year Clinical Follow-up. Orthop J Sports Med. 2021 Jan 12;9(1):2325967120973052. doi: 10.1177/2325967120973052. eCollection 2021 Jan.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hong-chul Lim, MD, PhD principal investigator
Korea University Guro Hospital
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cartistem and Microfracture treatment in people with Cartilage Injury and Osteoarthritis, run by Medipost Co Ltd. at 8 sites in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ICRS Cartilage Repair Assessment will follow to determine the appropriate grade. The treatment will be considered efficacious if the ICRS grade drops by at least 1 grade or more from baseline to week 48. (time frame: Week 0 and 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01041001, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2017.